Establishment as Shift Work Sleep Disorder Mouse Models: Toward the Investigation of Molecular Mechanism

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18866
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 58010:Medical management and medical sociology-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: GOTO MOTOHIDE 産業医科大学, 産業生態科学研究所, 助教 (90461558)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 概日リズム障害 / 交替勤務 / 動物モデル / がん悪液質

Outline of Final Research Achievements

Shift Work Sleep Disorder (SWSD) is one of the important health effects which could be a company’s liability. As the mice model of circadian rhythm disorder already reported differences in pathophysiological phenotype, we tried to establish a new mice model of SWSD, using cancer-induced cachexia model mice in which we have preliminarily found a change in active phase under normal light/dark cycle and also examined the pathophysiological mechanisms of this mice.Human stomach cancer cell lines implanted in mice demonstrated the reverse of day-night variation without synchronization of photoperiod and shortened free-running period. In both cancer-implanted mice and nocturnal mice, the number of c-Fos positive cells in the SCN peaked in the diurnal period and decreased in the nocturnal period.These results suggest that the cancer implantation may directly affect the possible regions which are received efferent signals of SCN and determine the diurnal/nocturnal behavior of mice.

Free Research Field

産業医学

Academic Significance and Societal Importance of the Research Achievements

研究成果から、マウスへのヒト胃がん細胞株移植はSCNからの投射を受け昼行性/夜行性を規定する神経領域に影響を与えている可能性が示唆された。昼行性ラット(ナイルグラスラット)でも、SCNの細胞活動日内変動パターンは、夜行性マウスと同様であることが報告されている。現時点では、マウスを含めた生物の昼行性/夜行性を規定するメカニズムの詳細は不明である。ヒト胃がん細胞株移植マウスを用いて、SCNからの投射を受けマウスの昼行性/夜行性を規定する神経領域を特定することができれば、生物の概日リズムに関する生理学的メカニズムの解明が進み、ひいては効果的な概日リズム睡眠障害治療薬の開発につながることが期待できる。